Glycogen Formation Research Articles

Effect of electrical stimulation on human skeletal muscle.

The acute and adaptive effects of electrical stimulation of the quadriceps muscle were investigated in healthy male volunteers. The acute effects, i.e., depletion of phosphagen and glycogen stores and formation of lactate as well as decreases in certain enzyme activities, were similar to those found earlier for intense muscular exercise. Intermittent electrical stimulation for 4 to 5 weeks did not cause any significant changes in enzyme activities, muscle fiber characteristics, or mitochondrial properties. A 4-week period of electrical stimulation resulted in improvements of muscle strength comparable to the results of a corresponding program of voluntary training. However, the effects of electrical stimulation appeared more "position-specific" and less "speed-specific" than those of voluntary training with slow isokinetic contractions.

Role of ovarian hormones in the long-term control of glucose homeostasis, glycogen formation and gluconeogenesis.

The effect of ovarian hormones on in vivo gluconeogenesis and glycogen deposition in liver, uterus, skeletal and cardiac muscle was studied. Ovariectomized adult female mice were treated with replacement doses of estradiol, progesterone, both hormones combined, or vehicle only for 15 weeks. Compared with intact control mice, ovariectomy increased gluconeogenesis and reduced the glycogen content of all tissues examined. Treatment with estradiol and progesterone, individually and in combination, increased tissue glycogen deposition. Estradiol alone consistently produced the greatest effect, except on hepatic glycogen, which was maximally increased by the combined estradiol-progesterone regimen. Estradiol markedly reduced gluconeogenesis, and this effect was antagonized by progesterone. The results indicate that the lower plasma glucose concentrations produced by ovarian steroids result in part from reduced glucose neoformation and greater storage of glycogen in liver and muscle tissues.

Effects of Glucose and Fructose Loading on Glycogenesis in Chicks Infected with Avian Tuberculosis

The chick was used as a rapid metabolic model to determine the fate of ingested fructose vs. glucose in noninfected chicks and in those subjected to the stress of avian tuberculosis. The chicks were crop-loaded with either a 72% fructose or glucose solution 21 and 28 days post TB inoculation and killed 2 and 4 hr after loading. In noninfected chicks, both sugars were rapidly converted to glycogen, and there was an interaction with time and the amount of glycogen formed from each sugar. Infection depressed glycogen formation from both fructose and glucose. While the total amount of glycogen formed from glucose could be directly correlated to increased liver size in the TB chicks loaded with glucose, in the chicks loaded with fructose less glycogen was formed even though liver size was increased as a result of the TB infection. The depression in glycogen formation was not related to the severity of the infection since the TB involvement was not the same in the two experiments conducted; but in both cases chicks loaded with fructose showed a greater reduction in the capacity of the liver to synthesize glycogen.

Clearance rates of metabolizable and nonmetabolizable sugars in insulin-infused dogs and in exercising dogs.

Dogs with indwelling arterial and venous catheters were trained to run on a treadmill (slope, 15% speed, 100 m/min). The clearance rates (CR) of 3H-inulin, 3-3Hglucose (G), 14C-L-arabinose (L-A), 14C-D-xylose (D-X), 14C-3-methyl-O-glucose (3-m-G) and 2-deoxy-glucose (2-d-G) were measured using the primed constant infusion tracer technics. With the exception of glucose, all substances were excreted in the urine; therefore the CR is the sum of the urinary clearance rate (UCR) plus the tissue clearance rate (tCR). By measuring CRinuMn and the concentration of 3H-inulin in the urine, the flow rate of urine and the UCR and tCR of the simultaneously infused 14C-sugars were calculated. Infusion of insulin (1.5 mU/kg min) and glucose (6 mg/kg min) into the resting dog raised plasma insulin to 60–40μU/ml at normoglycemia. The tCR of all sugars was increased: G>2-d-G>3-m-G>D-X>L-A. There was a great discrepancy between the phosphorylable (G, 2- d-G) and the nonmetabolizable sugars (3-m-G, D-X, LA). Insulin increased tCR of glucose almost threefold, and it was estimated that 27% of the increase could be ascribed to the unassisted direct effect of membrane- transport (3-m-G) and 55% if the glucose could be phosphorylated but not metabolized further (2-d-G). Exercise decreased plasma insulin by almost 50%, hepatic glucose production rose more than twofold, and the tCR-glucose more than 21/2-fold. The tCR of L-A remained unchanged and that of the other sugar derivatives was increased by the run in the following order G>2-d-G>3-m-G>D-X. It was estimated that only 16% of the increase of tCR-glucose could be ascribed to the effect of exercise on the membrane-transport if it was not assisted by the hexokinase, and 53% with the help of the enzyme but without the accelerated glycolysis. It is concluded that, under physiologic conditions, a relatively small fraction (16–20%) of the twoto threefold increase of glucose utilization can be ascribed to a direct membrane effect if the activity of flux-generating steps towards either glycogen formation (insulin) or glycolysis (exercise) is accelerated.

Arrays of glycogen granules in the axoplasm of peripheral nerves at pre-ovoid stages of Wallerian degeneration.

Phrenic and sciatic nerves of the rat were examined during the initial stages of Wallerian degeneration 4–48 h after axotomy about 5 mm below the level of transection. One of the first changes observed in transected axons was the appearance of glycogen granules and formation of clusters of particulate glycogen at the Schmidt-Lantermann incisures and at the nodes of Ranvier. Four hours after transection, glycogen granules were found at these sites mainly attached to the tubules of axoplasmic reticulum or dispersed in small clusters in the axoplasm. At later stages, glycogen particles increased in number and formed elongated clusters arrayed mostly longitudinally among axonal organelles filling stretches of axons about 2 μm long adjacent to the incisures and in nodal regions. The buld-up of glycogen clusters reached a peak at 22 h after axotomy, when longitudinal arrays of glycogen particles were found at about 70% of the incisures and nodes examined. The percentage of these sites containing glycogen clusters had already decreased 26 h after axotomy. When axonal degeneration advanced and axons contained only floculated material and swollen mitochondria, glycogen granules also disintegrated. It is of interest that glycogen particles accumulate in those regions of the internode where the axon will soon become disrupted during ovoid formation. The possible mechanisms leading to glycogen accumulation at these sites are discussed in relation to the active role of Schwann cells in Wallerian degeneration.

Restoration of glycogen from lactic acid in the anaerobic swimming muscle of plaice, Pleuronectes platessa L.

The conclusion from two in vivo experiments is that a significant proportion of the lactic acid, normally formed by glycolysis from glycogen and held in the muscle cells following exhausting exercise of the anaerobic swimming muscle of the teleost fish Pleuronectes platessa L, is converted by gluconeogenesis to form glycogen in the recovering muscle.In the first experiment a technique for measurement of [3H]glucose turnover in the plaice was developed and applied to measure turnover in resting and exhausted fish. It is concluded that insufficient glucose was moved through the circulation to account for the rate of glycogen formation observed in the recovering exhausted muscle.In the second experiment, an intramuscular injection of [14C]lactate to exhausted fish revealed a direct uptake of [14C]lactate by the recovering muscle cells, and the incorporation of substantial proportions of lactate into the restored glycogen. Simultaneous use of [3H]‐mannitol allowed measurement of the isotope distribution between extra‐ and intracellular spaces.

Hepatic glycogen formation by direct uptake of glucose following oral glucose loading in man.

The extent of direct uptake of glucose into hepatic glycogen following oral glucose loading in man is determined by mobilizing newly formed glycogen with a glucagon infusion in the immediately postabsorptive period. The amount of glucose flushed from liver glycogen is measured by using "out-of-steady-state" tracer turnover techniques. Following a 93 +/- 1 g load of glucose, at most 7.7 +/- 1 g of ingested glucose is recovered from glycogen. If the unlabelled glucose pool is taken into account, at most 10 g of available glucose can be said to be taken up directly into hepatic glycogen during the absorption of the glucose load.

Glycogen synthesis by hepatocytes from diabetic rats

Hepatocytes prepared from streptozotocin- and alloxan-diabetic rats starved for 24 h contain 0.5--2% wet wt. of glycogen. Glycogen synthesis in the hepatocytes from such rats, after prior depletion of the glycogen by glucagon injection, was studied. As distinct from cells from normal animals, there was no glycogen synthesis from glucose as sole substrate, even at concentrations of 60 mM. When supplied with glucose, a gluconeogenic precursor (lactate, dihydroxyacetone or fructose), and with glutamine there was concurrent synthesis of glucose and of glycogen. Without glutamine there was little or no glycogen synthesis. The rate of glycogen formation was in the same range as for cells from control rats. Glutamine addition markedly activated glycogen synthase in cells of starved diabetic rats, but there was no effect on phosphorylase. We obtained very little synthesis of glycogen with hepatocytes from fed diabetic rats, whereas with normal animals, synthesis by such cells equals or exceeds that obtained from starved rats. The conversion of synthase b (inactive) into the active form was studied in rat liver homogenates. The activation of the synthase in cells from starved diabetic rats is somewhat less than that from normal animals, but that from fed diabetic rats is markedly decreased compared with that in livers of fed control animals or that of starved diabetic animals.

Platelet glycolysis in platelet storage. III. The inability of platelets to utilize exogenous citrate.

The metabolism of exogenous citrate by freshly collected human platelets has been investigated by measuring the disappearance of citrate from platelet suspensions and by measuring the formation of CO2 and glycogen from purified radioactive citrate. These studies indicate that platelets do not have the capacity to metabolize exogenous citrate.

Glucose load diverts hepatic gluconeogenic product from glucose to glycogen in vivo.

Intravenous or oral administration of concentrated glucose solution into fasted rats simultaneously injected with 14C-bicarbonate resulted in an inhibition of [14C]glucose release into the blood and in an accelerated [14C]glycogen formation associated with glycogen synthetase activation and phosphorylase inactivation in the liver. The specific activity of glycogen was much higher than that of blood glucose after the glucose load, indicating that glycogen originated from gluconeogenesis rather than blood glucose. These metabolic changes induced by the glucose load were not mediated by endogenous insulin because they were observed to the same extent in rats treated with anti-insulin serum. However, they were mostly, if not totally, abolished by adrenalectomy, which suppressed gluconeogenesis and glycogenesis. Glucose tolerance was markedly impaired not only by anti-insulin serum, which inhibits peripheral glucose utilization, but also by adrenalectomy, which affects hepatic metabolism. It is concluded that a glucose load diverts the final product of hepatic gluconeogenesis from blood glucose to liver glycogen; these metabolic changes in the liver are an important determinant of glucose tolerance.

Glycogen-lead relationship in the earthworm Dendrobaena rubida from a heavy metal site.

Control individuals contained no lead in the chloragocytes but high alpha-glycogen rosette reserves. Starvation of contaminated earthworms for 4d caused a lead loss and the chlorgocytes possessed fewer debris vesicles than those of unstarved worms, suggesting that the debris vesicles may be the route for at least some of the lead loss. No glycogen deposits were observed in the chloragocytes of starved or unstarved earthworms from contaminated soil. Maintenance of contaminated earthworms in potting compost caused lead losses similar to those sustained by starvation, but the chloragocyte cytoplasm possessed beta-glycogen reserves. Specimens maintained in lead-spiked potting compost showed lead levels similar to those of earthworms taken directly from contaminated soil. No beta-glycogen accumulations were observed under this enriched regime. Although the possible interference of lead in carbohydrate metabolism is discussed, the results do not wholly support metabolic inhibition by lead. It is hypothesised that lead sequestration is energy-demanding and that in the absence of an energy-rich diet glycogen stores fail to accumulate. In the presence of an organic-rich medium, elevated lead levels preclude glycogen formation, because of the high sequestration-demand, but at lower lead levels beta-glycogen deposits occur if a high organic diet is available.

Acute effects of glucose-insulin-potassium infusion on myocardial substrates, coronary blood flow and oxygen consumption in man

To determine whether myocardial oxygen consumption (MVO 2) might be reduced when myocardial substrate uptake is changed from predominantly lipid to predominantly carbohydrate, measurements of arterialcoronary sinus glucose, lactate, free fatty acids, oxygen, carbon dioxide and coronary sinus blood flow (by thermodilution) were obtained in 13 fasting patients. Measurements were initially made in a basal control state and then repeated at 10, 20 and 30 minutes during an infusion of glucose-insulin-potassium. After 30 minutes of infusion, there was a three-fold increase in myocardial glucose uptake (44 ± 10 to 145 ± 19 +μmoles/min [mean ± standard error of the mean], P < 0.01), a two-fold increase in myocardial lactate uptake (35 ± 4 to 77 ± 10 μmoles/min, P < 0.001) and a 75 percent decrease in myocardial free fatty acid uptake (34 ± 5 to 9 ± 3 μmoles/min, P < 0.01). Cardiac respiratory quotient rose from 0.70 ± 0.05 to 0.93 ± 0.08 ( P < 0.001). Sum of oxygen extraction ratios for glucose and lactate rose from 51 ± 7 percent at control to 155 ± 22 percent at 30 minutes of infusion ( P < 0.001) and suggested that much of the enhanced myocardial carbohydrate uptake met a nonoxidative fate, such as glycogen formation. During glucose-insulin-potassium infusion, arterial-coronary sinus oxygen decreased by 13 percent, coronary sinus blood flow increased by 12 percent and MVO 2 was unchanged. The increase in coronary sinus blood flow was associated with a 13 percent decrease in coronary vascular resistance and a small, but significant, increase in serum osmolarity (289 ± 3 to 299 ± 3 mOsm/liter, P < 0.001). It is concluded that glucose-insulin-potassium infusion, while causing prompt alteration in myocardial substrate utilization from lipid to carbohydrate, produces no significant measurable change in myocardial oxygen consumption. However, such infusion is accompanied by a measurable increase in coronary sinus blood flow and a decrease in coronary vascular resistance.

Alteration by halothane of glucose and glycogen metabolism in rat skeletal muscle.

Exposure of resting rat diaphragm for one hour in vitro to halothane (1-1.5, 2-2.5 and 4-4.5 per cent in oxygen) produced significant alterations of intracellular glucose disposition. Glycolysis (as measured by lactate production) increased, while glycogen formation was inhibited in a dose-related fashion. Net glucose uptake was unaffected by the anesthetic except during exposure to 4-4.5 per cent halothane, when 14 per cent depression of uptake was found. Total glycogen content decreased, due mainly to the inhibition of glycogen synthesis and to some extent to a stimulation of glycogenolysis. The anesthetic did not interfere with the effect of insulin on glucose uptake or the intracellular disposition of glucose. Creatine phosphate concentrations decreased following exposure of diaphragm to 1-1.5, 2-2.5 and 4-4.5 per cent halothane, while the adenosine triphosphate concentration declined after exposure to 4-4.5 per cent only. Although the mechanism(s) whereby halothane alters glucose and glycogen metabolism are unknown, it is possible that the anesthetic acts primarily by affecting membranes containing enzymes involved in the metabolism of glycogen.

Stimulation of hepatic glycogen synthesis by amino acids.

Hepatocytes isolated from livers of fasted rats form little glycogen from glucose or lactate at concentrations below 20 mM. Glycogen is formed in substantial quantities at a glucose concentration of 60 mM. In the presence of 10 mM glucose, 20-30% as much glycogen as glucose is formed from fructose, sorbitol, or dihydroxyacetone. The addition of either glutamine, alanine, or asparagine stimulates the formation of glycogen from lactate 10- to 40-fold. The formation of glucose and glycogen is then about equal, and glycogen deposition in hepatocytes is similar to rates attained in vivo after fasted rats are refed. The amino acids stimulate 1.5- to 2-fold glycogen synthesis from fructose, and 2- to 4-fold synthesis from dihyDROXYACETONE. Ammonium chloride is about one-half as effective as amino acids in stimulating glycogen synthesis when glucose with lactate are substrates. It increased glycogen synthesis 25-50% from fructose but inhibited synthesis from dihydroxyacetone plus glucose.

Metabolic effects of insulin in the European eel, Anguilla anguilla L

Eels were injected intraperitoneally with insulin (100 IU/kg) and during 14 days the effects on different metabolites in blood, liver and muscle were studied. Exogenous insulin had a marked effect on carbohydrate metabolism. The observed changes (hypoglycemia, depletion of hepatic glycogen and an initial increase in muscle glycogen formation) indicate that insulin in eels induces effects on carbohydrate metabolism qualitatively similar to those found in mammals. Insulin also appears to have an important function in the regulation of lipid metabolism in eels, indicated by a rapid decrease in plasma FFA and a somewhat delayed decrease in other blood lipids. Protein metabolism and plasma inorganic ions were only slightly affected after insulin injection.

Nutritional changes in patients with cancer

At some time during the clinical course of any patient with metastatic malignant disease, one frequently sees the symptom complex of anorexia, asthenia, loss of body tissues and inability to conserve normal regulatory functions. This common host response bears no positive correlation to the amount, type of site of neoplastic tissue and patients may have obvious widespread tumors without such manifestations. However, when this systematic response occurs, it is readily recognized by the clinician experienced in this area that uncontrolled tumor growth is occurring and that unless such cancerous growth can be inhibited, progressive inanition and ultimate death will occur. Studies designed to define the metabolic changes that are present in the above clinical syndrome must take into account the subnormal nutritional status of such patients. Since anorexia is invariably present, the stoichiometric regulation and metabolic adaptions which are normally seen with restricted protein and caloric intake have been the subject of consideration. Semistarvation normally results in diminished adenosine triphosphate (ATP) requirement, since the formation of glycogen, fatty acids and triglycerides which result from transient excesses of foodstuffs are diminished. This in turn leads to a decrease in oxygen consumption. While transient increase in gluconeogenesis may be seen, the long term adjustment is that of increased mobilization of fatty acids from adipose tissue with diminished glucose production from amino acids.’ Conservation of the latter ingredient primarily for key enzyme synthesis is necessary for survival (e.g. those enzymes related to fatty acid oxidation). A considerable amount of older work has suggested that the normal decrease in oxidative metabolism does not take place in patients with cancer.2.3 Calculations of energy expenditure, determinations of basal oxygen consumption and CO2 production all seem inappropriately high for the condition of study. In a control series vs five subjects with metastatic malignant disease, the total mean CO2 production in the basal state was 7.6 mm/kg/hr vs 8.3 mml/kg/hr (malignant disease). Viewing the data as such, the mean difference between the two groups is only 10% and of little significance. Yet all subjects in the neoplastic group, though roughly matched in weight to the control group, had lost body weight and had lower caloric intakes at the time these studies were done. When viewed in this context, i.e. the nutritional status of the patients, the data become more meaningful. Studies of the metabolic mixture resulting in CO, production, however, show that normal proportions of glucose and fatty acid are oxidized in the fasting state.4 New glucose production in the postabsorptive state, as determined by tracer technique, has shown a mean value of 5.9g/hr for the control group and 6.6g/hr in the group with cancer.’ Even though the latter group tended to have lower body weights, new glucose production, presumably largely from amino acid precursors, was comparable or slightly enhanced over that of the control group. Normally about 17% of the lactate produced by glycolysis is reconverted into glucose.

Electron microscope study of vitellogenesis in Glaridacris catostomi (Cestoidea: Caryophyllidea)

Swiderski Z. and Mackiewicz J. S. 1976. Electron microscope study of vitellogenesis in Glaridacris catostomi (Cestoidea: Caryophyllidea). International Journal for Parasitology 6: 61–73. Mature vitelline follicles consist of cells in various stages of development, progressing from immature cells of gonial type near the periphery to mature ones toward the centre. Maturation, completed before the cell leaves the follicle, is characterized by: increase in cell volume; increase in nuclear surface area restoring the N/C ratio; nucleolar transformation; extensive development of large parallel cisternae of granular endoplasmic reticulum, the shell-protein producing units; development of Golgi complexes engaged in shell globule formation; formation and storage of glycogen in the cytoplasm; simultaneous, independent formation and storage of intranuclear glycogen; progressive increase in the number and size of shell globule clusters; and disintegration of endoplasmic reticulum, degenerative changes, and accumulation of glycogen and shell globule clusters within the cytoplasm associated with a massive accumulation of glycogen in the nucleus. The functional significance of the large amount of nuclear and cytoplasmic glycogen and numerous shell globule clusters is analyzed. Vitellogenesis in G. catostomi is compared with that in other cestodes and trematodes. Some conclusions, concerning the interrelationship between the vitellogenesis pattern and the type of embryogenesis following it, are drawn and discussed.

Cytochemistry of late ovarian chambers of Drosophila melanogaster.

Late ovarian chambers of Drosophila melanogaster have been examined by ultrastructural cytochemistry in an attempt to characterize some of the transformations which precede the completion of oogenesis. From stage 11 onward peroxidase activity is present in the endoplasmic reticulum of both nurse cells and oocyte, as well as in the egg-covering precursors of the columnar follicle cells. Catalase activity is restricted to the very last stages of oogenesis (stage 13-14) and appears to be located in membrane-bound organelles of the ooplasm which are continuous with the endoplasmic reticulum. Because of the presence of catalase as well as by their structural appearance, these organelles are to be identified as microperoxisomes. Catalase activity becomes cytochemically detectable in the ooplasm somehow in coincidence with the formation of glycogen. Furthermore, glycogen is first formed in intimate association with alpha-1 yolk platelets. On the basis of these findings it is suggested that glycogen synthesis occurs by a process of gluconeogenesis.

Carbohydrate metabolism in perfused livers of adrenalectomized and steroid-replaced rats

In livers from fasted rats perfused with bicarbonate buffer containing bovine albumin and erythrocytes, adrenalectomy decreased glycogen levels and glucose production, impaired the incorporation of 14C from [14C]lactate into glucose or glycogen, and decreased the activity of the active (I) form of glycogen synthase. Cortisol treatment restored gluconeogenesis after 1 h and glycogen synthesis after 2 h. Adrenalectomy did not alter the production of glucose or lactate or the levels of gluconeogenic intermediates in livers from fasted rats perfused with fructose, but reduced the formation of glycogen from this substrate. Adrenalectomy increased the levels of lactate and decreased the levels of P-pyruvate and subsequent intermediates in the gluconeogenic pathway. These changes were reversed by cortisol treatment. It is concluded that glucocorticoids support gluconeogenesis and glycogen synthesis in livers from fasted rats primarily by facilitating a reaction(s) located between pyruvate and P-pyruvate in the gluconeogenic pathway and by promoting the conversion of inactive to active glycogen synthase.

Metabolic and electrolyte changes produced by lithium ions in the isolated rat diaphragm

The effects of lithium ions on glucose metabolism and the tissue content of monovalent cations were studied in rat hemidiaphragms incubated in vitro. The entrance of lithium ions into the cell was associated with an increase in the rate of glucose utilization and glycogen synthesis. As lithium was taken up by the tissue, there was a concomitant loss of potassium. The loss of potassium could not account for the stimulation of glucose metabolism produced by lithium and it was concluded that lithium ions per se increased glucose uptake and particularly glycogen synthesis. Preincubation of hemidiaphragms in media containing different concentrations of lithium ions resulted in an increase in the rate of glycogen synthesis during a subsequent incubation in the absence of lithium. The stimulation of glycogen formation was directly related to the tissue content of lithium. Lithium ions did not significantly alter the cyclic AMP content of the tissues under conditions at which the rate of glucose metabolism was markedly enhanced.